Canakinumab in Patients With COVID-19 and Type 2 Diabetes - CanCovDia Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 116
- 试验地点
- 9
- 主要终点
- unmatched win ratio after treatment with canakinumab compared to Placebo (composite endpoint)
研究概览
简要总结
The purpose of this study is to evaluate whether Canakinumab has beneficial effects on patients with Type 2 diabetes mellitus and coronavirus disease 19 (COVID19).
详细描述
Patients with a metabolic syndrome (overweight, diabetes, hypertension) have a particularly bad outcome if infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). This may be explained by an over-activation of the Interleukin-1 (IL-1) beta system. Metabolic stress (increased glucose and lipid levels) induces NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) -mediated IL-1beta secretion. SARS-CoV2 also activates NLRP3. Therefore, the study proposes that metabolic stress in patients with overweight and diabetes potentiates COVID-19 induced hyperinflammatory syndrome leading to excess mortality in these vulnerable patients. Canakinumab (Ilaris®) is a recombinant, human monoclonal antibody antagonizing IL-1beta by blocking IL-1beta activity. The aim of the study is to investigate the effect of canakinumab in type 2 diabetic patients with COVID-19.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of type 2 diabetes mellitus
- •Body mass index > 25 kg/m² (overweight)
- •Hospitalized with COVID-19
排除标准
- •Suspected or known untreated active bacterial, fungal, viral, or parasitic infection with the exception of COVID-19
- •Treatment with immunomodulators or immunosuppressant drugs, including but not limited to tocilizumab, tumor necrosis factor (TNF) inhibitors and anti-IL-17 agents within 5 half-lives or 30 days (whichever is longer) prior to randomization with the exception of anakinra which is excluded within 5 half-lives only. Note: Immunomodulators (topical or inhaled) for asthma and atopic dermatitis, and corticosteroids (any route of administration) such as dexamethasone are permitted.
- •History of hypersensitivity to canakinumab or to biologic drugs
- •Neutrophil count <1000/mm3
- •Pregnant or nursing (lactating) women
- •Participation in another study with investigational drug within the 30 days preceding and during the present study-
研究组 & 干预措施
placebo treatment arm
placebo treatment
干预措施: Placebo (Drug)
active treatment arm
Treatment with Canakinumab i.v. administered over 2 hours
干预措施: Canakinumab (Drug)
结局指标
主要结局
unmatched win ratio after treatment with canakinumab compared to Placebo (composite endpoint)
时间窗: within 4 weeks after treatment with canakinumab or placebo
Treatment and placebo will be compared on the basis of the unmatched win-ratio approach of Pocock. When comparing two patients, the winner will be determined by the first component in which the two patients differ (4 weeks after randomization): 1. longer survival time 2. longer ventilation-free time 3. longer ICU-free time 4. shorter hospitalization time If there is no difference between treatment and Placebo: the win ratio is 1. If there is a difference between treatment and Placebo: the win ratio is not 1.
次要结局
- Prolonged hospital stay(>3 weeks)
- Change in ratio to baseline in the glycated hemoglobin(Baseline, Day 29 and Day 90)
- Change in ratio to baseline in the Natriuretic peptide (NTproBNP)(Baseline, Day 29 and Day 90)
- Number of antidiabetic treatment at Day 29(Day 29)
- Time to clinical improvement(From randomization up to 4 weeks)
- Admission to intensive care unit (ICU)(4 weeks)
- Change in ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)(Baseline, Day 29 and Day 90)
- Type of antidiabetic treatment at Day 29(Day 29)
- Death rate(4 weeks)
- Secondary worsening of disease(4 weeks)
- Change in ratio to baseline in the fasting glucose(Baseline, Day 29)
- Change in ratio to baseline in the fasting insulin(Baseline, Day 29)
- Change in ratio to baseline in the fasting c-peptide(Baseline, Day 29)
- Ratio to baseline in the C-reactive protein (CRP)(Baseline, Day 29 and Day 90)
- Change in ratio to baseline in the D-dimer(Baseline, Day 29)
- Type of antidiabetic treatment at three months(Month 3)
- Number of antidiabetic treatment at three months(Month 3)